Intake of alpha-linolenic acid and other fatty acids in relation to the risk of bladder cancer: results from the New Hampshire case-control study.

The role of dietary fat in bladder cancer aetiology is currently unclear due to few studies, equivocal findings and a lack of information on important dietary fatty acids. The aim of the present study was to investigate the association between the intake of major dietary fats and fatty acids and the risk of bladder cancer. A case-control study was conducted in New Hampshire, USA. Dietary data were collected from 322 cases and 239 controls, and OR and 95 % CI were calculated using unconditional logistic regression. Adjustment was made for potential confounders: sex, age, smoking status, pack-years smoked, cholesterol and energy intake. Statistically significant reduced odds of bladder cancer were observed for high intakes (highest quartile v. lowest quartile) of alpha-linolenic acid (ALA) (OR 0.26, 95 % CI 0.10, 0.65; P for trend = 0.01) and vegetable fat (OR 0.39, 95 % CI 0.18, 0.86; P for trend = 0.03). Borderline statistically significant reduced odds were detected for polyunsaturated fat (OR 0.43, 95 % CI 0.19, 0.98; P for trend = 0.07) and linoleic acid (OR 0.43, 95 % CI 0.19, 0.96; P for trend = 0.06). These fats and fatty acids were highly correlated and following adjustment for each other, the only potential inverse association to remain was for ALA. The present findings suggest that ALA may have a protective role against developing bladder cancer; however, further investigation and replication in other epidemiological studies are required. Future research should focus on the type, source and quantities of different dietary fatty acids consumed

Integrated longitudinal analysis of adult grade 4 diffuse gliomas with long-term relapse interval revealed upregulation of TGF-β signaling in recurrent tumors.

Adult-type diffuse gliomas, CNS WHO grade 4 are the most aggressive primary brain tumors and represent a particular challenge of therapeutic intervention. In a single-center retrospective study of matched pairs of initial and post-therapeutic glioma cases with a recurrence period greater than one year, we performed whole exome sequencing combined with mRNA and microRNA expression profiling to identify processes that are altered in recurrent gliomas. Mutational analysis of recurrent gliomas revealed early branching evolution in seventy-five percent of patients. High plasticity was confirmed at the mRNA and miRNA levels. SBS1 signature was reduced and SBS11 was elevated, demonstrating the effect of alkylating agent therapy on the mutational landscape. There was no evidence for secondary genomic alterations driving therapy resistance. ALK7/ACVR1C and LTBP1 were upregulated, whereas LEFTY2 was downregulated, pointing towards enhanced Tumor Growth Factor β (TGF-β) signaling in recurrent gliomas. Consistently, altered microRNA expression profiles pointed towards enhanced Nuclear Factor Kappa B and Wnt signaling that, cooperatively with TGF-β, induces epithelial to mesenchymal transition (EMT), migration and stemness. TGF-β-induced expression of pro-apoptotic proteins and repression of anti-apoptotic proteins were uncoupled in the recurrent tumor. Our results suggest an important role of TGF-β signaling in recurrent gliomas. This may have clinical implication, since TGF-β inhibitors have entered clinical phase studies and may potentially be used in combination therapy to interfere with chemoradiation resistance. Recurrent gliomas show high incidence of early branching evolution. High tumor plasticity is confirmed at the level of microRNA and mRNA expression profiles